Combining Clemastine and Aerobic Exercise to Treat Cognitive Dysfunction in Schizophrenia by Targeting Myelin Plasticity (OligoTreat)

Phase 1

• Conditions: Schizophrenia; MedDRA version: 20.0Level: PTClassification code 10039626Term: SchizophreniaSystem Organ Class: 10037175 - Psychiatric disorders; Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

• Registration Number: EUCTR2022-000054-28-DE
• Lead Sponsor: Klinikum der Universität München

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-01-27
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1.Written informed consent obtained from the participant prior to performing any protocol-related procedures, including screening evaluations
2. DSM-V diagnosis of schizophrenia or schizophrenia-spectrum disorder according to MINI interview
3.Age between 18 and 65 years
4.Total Positive and Negative Syndrome Scale (PANSS) score = 75 at V0
5.Stable antipsychotic treatment dose for at least one week prior to inclusion
6.Stable CNS-active treatment substance and dose (e.g. antidepressants and mood stabilizers) for at least one week prior to inclusion
7.Female participants with reproductive potential must have a negative beta-HCG serum pregnancy test using a pregnancy test strip as part of the screening visit
8.Female participants with reproductive potential must have a negative serum pregnancy test within seven days prior to randomization
9.Male participants and female participants who are not capable of bearing children or who use a method of contraception that is medically approved by the health authority of the respective country at screening

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 88
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

1.Patients who are unable to give informed consent
2.Coercive treatment at the time of study inclusion
3.Treatment-naïve schizophrenia defined as cumulative treatment with an antipsychotic agent lifetime for <30 days
4.Insufficient understanding of the German language
5.Patients with primary active (moderate or severe) substance use disorder (other than nicotine) according to MINI interview (DSM-V): patients fulfilling early (>3 months) or sustained (>12 months) remission criteria and/or with low severity of substance use disorder according to MINI are eligible for the study
6.Known clinically relevant CNS disorder(s), such as epilepsy or history of seizures
7.Concomitant use of any other putative remyelinating therapy as determined by investigator
8.Co-occurrent unstable somatic condition
9.Known porphyria
10.Known narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, prostatic hypertrophy with urinary retention and bladder neck obstruction
11.Current treatment with agents with strong anticholinergic properties, such as MAO-inhibitors, opioid antagonists, clozapine at the time of study inclusion
12.Known intolerance, allergy/contraindications to one of the study drugs or any of the excipients or other agents with similar chemical properties as the study drugs (such as other arylalkylamine antihistamines)
13.Clinically relevant liver and/or renal impairment (serum creatinine >1.5mg/dl or eGFR<30 ml/min/1.73 m2 at screening, AST or ALT > 2-times the upper limit of normal at screening)
14.Current treatment with macrolide-antibiotics (such as erythromycin, clarithromycine) or azole-type antimycotics
15.Clinically relevant cardiac comorbidities (i.e. Long QT-syndrome)
16.Current hypokalaemia and/or clinically relevant hyponatraemia at screening
17.Patient-reported hereditary galactose-intolerance and/or Lapp lactose-deficiency, lactose intolerance and/or glucose-galactose malabsorption
18.Pregnancy or breast-feeding
19.Concurrent enrolment in another clinical trial where the participant is receiving an IMP or participation in another clinical trial with IMP during the last 30 days before inclusion or 7 half-lives of previously used IMP, whichever is longer.
20.For the optional MRI assessments: potential MRI contraindication(s)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective 1 is the change in Global Assessment of Functioning (GAF) scores from the start of the intervention period (V1.1) to primary outcome visit after 90-93 days of treatment (V2).<br>The primary objective 2 is the change in working memory performance assessed by the n-back test (2-back level, d-prime) from V1.1 to V2. <br>;Secondary Objective: •Change in total PANSS scores at V2 compared to baseline<br>•Change in Clinical Global Impression (CGI) rating scale at V2 compared to baseline <br>•Change in remission criteria (Andreasen Remission criteria”) status from V2 compared to baseline<br>•Change in GAF and n-back scores (2-back, d-prime) from V3 compared to V2<br><br>;Primary end point(s): 1. Absolute change in working memory performance assessed by the n-back test (2-back, d-prime) after 90-93 days of treatment.<br>2. Absolute change in GAF score after 90-93 days of treatment. <br>;Timepoint(s) of evaluation of this end point: Baseline (V1.1) to 90-93 days (V2).